Dimpling of the skin or the “mattress phenomenon” of the thighs and buttocks is commonly referred to as cellulite. This condition is common and appears in otherwise healthy individuals afflicting women much more frequently than men. Over the counter topical therapies abound for the elimination of cellulite. These products and other over the counter topical applications have proved to be useless, costly, and in fact, have never undergone proper placebo controlled clinical trials. Recent randomized, placebo controlled trials of topical retinol and retinol-containing caffeine and ruscogenine have also failed to show merit for the elimination of cellulite.
If the treatment of cellulite is to be successful, then the basic pathophysiology of the condition requires clear definition. It was only in 1998 that Rosenbaum, et al. undertook an investigation of the morphology and biochemistry of cellulite (Rosenbaum, M., Prieto, V., Hellmer, J., Boschmann, M., Krueger, J., Leibel, R. L., Ship, A. G., An Exploratory Investigation of the Morphology and Biochemistry of Cellulite, Plastic & Reconst Surg 101(7): 1934-9, 1998). Seven healthy adult subjects, five women and two men, four affected, three unaffected, underwent sonography of the thigh, measurement of regional in vivo subcutaneous adipose tissue metabolism and full thickness wedge biopsy of the thigh under local anesthesia. The presence of cellulite was defined as evidence of dimpling of the skin of the posterolateral thigh. Any continuous area of skin at least 3 cm in diameter in which no dimpling was evident was designated as unaffected. In all affected individuals studies were performed to include both affected and unaffected areas of the thigh. Microscopic examination of the wedge biopsies and in vivo sonographic examination of the thigh both showed a diffuse pattern of extrusion of underlying adipose tissue into the reticular dermis in affected, but not unaffected, subjects. The study also demonstrated that women had a diffuse pattern of irregular and discontinuous connective tissue immediately below the dermis but the same layer of connective tissue was smooth and continuous in men. This connective tissue layer was more irregular and discontinuous in affected vs. unaffected individuals. No significant differences were noted in subcutaneous adipose tissue morphology, lipolytic responsiveness, or regional blood flow between affected and unaffected sites within individuals. This study demonstrated that there is a sexual dimorphism in the structural characteristics of the dermal connective tissue that pre-disposes women to develop the irregular extrusion of adipose tissue into the dermis which characterized cellulite. This study concluded that there was no evidence of any primary role for adipose tissue physiology, blood flow or adipose tissue biochemistry in the etiology of cellulite but that the connective tissue of the female thigh and buttocks is structured to accentuate differences in small sub-dermal adipose tissue deposits.
This conclusion was substantiated by the work of Pierard, et al. who examined 39 autopsy specimens microscopically (Pierard-Franchimont, C., Pierard G. E., Henry, F., Vroome, V. & Cauwenbergh, G. A Randomized, Placebo-Controlled Trial of Topical Retinol in the Treatment of Cellulite, Amer. J. Clin. Dermatology, 1(6):369-74, 2000). Their control group consisted of four adult women and eleven adult men showing no evidence of cellulite. They state that the lumpy aspect of the dermal hypodermal interface appeared to represent a gender linked (female) characteristic of the thighs and buttocks. Cellulite was identified by this mattress phenomenon microscopically and presented as focally enlarged fibrosclerotic strands partitioning the subcutis. They speculated that these structures might represent a reactive process to sustained hypodermal pressure caused by fat accumulation.
In a more recent study by Querleux, et al. the anatomy and physiology of subcutaneous adipose tissue in relation to sex and the presence of cellulite were studied by in vivo magnetic resonance imaging and spectroscopy (Querleux, B., Cornillon, C., Jolivet, O., Bittoun, J., Anatomy and Physiology of Subcutaneous Adipose Tissue by in vivo Magnetic Resonance Imaging and Spectroscopy: Relationships with Sex and Presence of Cellulite, Skin Research And Tech 8(2):118-124, May 2002). These authors concluded that 3D reconstruction of the fibrous septae network showed a higher percentage of septae in the direction perpendicular to the skin surface in women with cellulite.
There remains no effective treatment of cellulite up to date. It is the object of this invention to provide such methods for treatment of cellulite.